Abstract Hepatocellular carcinoma (HCC) is a disease of growing incidence globally, including in the US (by 3% per year). With the recent success of anti-viral therapies, the etiology of HCC in the American population is projected to shift from viral (HBV, HCV) hepatitis to primarily fatty liver disease in the near future. Currently, only one effective systemic therapy has been developed for HCC ? the multi-kinase inhibitor sorafenib. The development of more selective molecularly targeted therapies has so far been unsuccessful in this disease. This failure is due in part to the lack of a preclinical, patient-derived xenograft (PDX)- enabling HCC tumor bank drawn from an American HCC patient population to help patient selection and model new therapies. In addition, modeling underlying liver disease has rarely been pursued in preclinical drug development. PDX-enabling tumor banks exist in Asia, but tend to be from viral and alcohol-driven disease, as opposed to obesity, which is the driver of growing incidence in the West. Massachusetts General Hospital (MGH) has begun collecting primary patient HCC tumors from surgeries performed in Boston and will partner with Woodland Pharmaceuticals, the applicant, to expand these into a PDX resource better enabling new HCC therapy development. Woodland will expand the tumors to up to five passages in mice and then characterize the passages for drug sensitivity, both in vitro and in vivo to a panel of drugs. Demonstration of stable expansion will lead to a phase 2 application to further expand and characterize the HCC tumor bank (including tracking of patient treatment and outcomes at the academic site), in models with underlying liver disease, in readiness for PDX service commercialization in the USA.